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Journal of Personalized Medicine Jun 2022Pharmacogenetics research on leukotriene modifiers (LTMs) for asthma has been developing rapidly, although pharmacogenetic testing for LTMs is not yet used in clinical...
Pharmacogenetics research on leukotriene modifiers (LTMs) for asthma has been developing rapidly, although pharmacogenetic testing for LTMs is not yet used in clinical practice. We performed a systematic review and meta-analysis on the impact of pharmacogenomics on LTMs response. Studies published until May 2022 were searched using PubMed, EMBASE, and Cochrane databases. Pharmacogenomics/genetics studies of patients with asthma using LTMs with or without other anti-asthmatic drugs were included. Statistical tests of the meta-analysis were performed with Review Manager (Revman, version 5.4, The Cochrane Collaboration, Copenhagen, Denmark) and R language and environment for statistical computing (version 4.1.0 for Windows, R Core Team, Vienna, Austria) software. In total, 31 studies with 8084 participants were included in the systematic review and five studies were also used to perform the meta-analysis. Two included studies were genome-wide association studies (GWAS), which showed different results. Furthermore, none of the SNPs investigated in candidate gene studies were identified in GWAS. In candidate gene studies, the most widely studied SNPs were ALOX5 (tandem repeats of the Sp1-binding domain and rs2115819), LTC4S-444A/C (rs730012), and SLCO2B1 (rs12422149), with relatively inconsistent conclusions. LTC4S-444A/C polymorphism did not show a significant effect in our meta-analysis (AA vs. AC (or AC + CC): −0.06, 95%CI: −0.16 to 0.05, p = 0.31). AA homozygotes had smaller improvements in parameters pertaining to lung functions (−0.14, 95%CI: −0.23 to −0.05, p = 0.002) in a subgroup of patients with non-selective CysLT receptor antagonists and patients without inhaled corticosteroids (ICS) (−0.11, 95%CI: −0.14 to −0.08, p < 0.00001), but not in other subgroups. Variability exists in the pharmacogenomics of LTMs treatment response. Our meta-analysis and systematic review found that LTC4S-444A/C may influence the treatment response of patients taking non-selective CysLT receptor antagonists for asthma, and patients taking LTMs not in combination with ICS for asthma. Future studies are needed to validate the pharmacogenomic influence on LTMs response.
PubMed: 35887565
DOI: 10.3390/jpm12071068 -
Clinical Pharmacology and Therapeutics Dec 2022The objective of this study was to evaluate the evidence on cost-effectiveness of pharmacogenetic (PGx)-guided treatment for drugs with Clinical Pharmacogenetics...
The objective of this study was to evaluate the evidence on cost-effectiveness of pharmacogenetic (PGx)-guided treatment for drugs with Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines. A systematic review was conducted using multiple biomedical literature databases from inception to June 2021. Full articles comparing PGx-guided with nonguided treatment were included for data extraction. Quality of Health Economic Studies (QHES) was used to assess robustness of each study (0-100). Data are reported using descriptive statistics. Of 108 studies evaluating 39 drugs, 77 (71%) showed PGx testing was cost-effective (CE) (N = 48) or cost-saving (CS) (N = 29); 21 (20%) were not CE; 10 (9%) were uncertain. Clopidogrel had the most articles (N = 23), of which 22 demonstrated CE or CS, followed by warfarin (N = 16), of which 7 demonstrated CE or CS. Of 26 studies evaluating human leukocyte antigen (HLA) testing for abacavir (N = 8), allopurinol (N = 10), or carbamazepine/phenytoin (N = 8), 15 demonstrated CE or CS. Nine of 11 antidepressant articles demonstrated CE or CS. The median QHES score reflected high-quality studies (91; range 48-100). Most studies evaluating cost-effectiveness favored PGx testing. Limited data exist on cost-effectiveness of preemptive and multigene testing across disease states.
Topics: Humans; Pharmacogenomic Testing; Pharmacogenetics; Cost-Benefit Analysis; Warfarin; Carbamazepine
PubMed: 36149409
DOI: 10.1002/cpt.2754 -
Pharmacology Research & Perspectives Dec 2023Pharmacogenomics remains underutilized in clinical practice, despite the existence of internationally recognized, evidence-based guidelines. This systematic review aims... (Review)
Review
Pharmacogenomics remains underutilized in clinical practice, despite the existence of internationally recognized, evidence-based guidelines. This systematic review aims to understand enablers and barriers to pharmacogenomics implementation in pediatric oncology by assessing the knowledge, attitudes, and practice of healthcare professionals and consumers. Medline, Embase, Emcare, and PsycINFO database searches identified 146 relevant studies of which only three met the inclusion criteria. These studies reveal that consumers were concerned with pharmacogenomic test costs, insurance discrimination, data sharing, and privacy. Healthcare professionals possessed mostly positive attitudes toward pharmacogenomic testing yet identified lack of experience and training as barriers to implementation. Education emerged as the key enabler, reported in all three studies and both healthcare professionals and consumer groups. However, despite the need for education, no studies utilizing a pediatric oncology consumer or healthcare professional group have reported on the implementation or analysis of a pharmacogenomic education program in pediatric oncology. Increased access to guidelines, expert collaborations and additional guidance interpreting results were further enablers established by healthcare professionals. The themes identified mirror those reported in broader pediatric genetic testing literature. As only a small number of studies met inclusion criteria for this review, further research is warranted to elicit implementation determinants and advance pediatric pharmacogenomics.
Topics: Humans; Child; Pharmacogenetics; Health Knowledge, Attitudes, Practice; Health Personnel; Medical Oncology; Neoplasms
PubMed: 38013228
DOI: 10.1002/prp2.1150 -
Pharmaceutics Jun 2022This systematic review summarizes the impact of pharmacogenetics on the effect and safety of non-steroidal anti-inflammatory drugs (NSAIDs) and antidepressants when used... (Review)
Review
BACKGROUND
This systematic review summarizes the impact of pharmacogenetics on the effect and safety of non-steroidal anti-inflammatory drugs (NSAIDs) and antidepressants when used for pain treatment.
METHODS
A systematic literature search was performed according to the preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines regarding the human in vivo efficacy and safety of NSAIDs and antidepressants in pain treatment that take pharmacogenetic parameters into consideration. Studies were collected from PubMed, Scopus, and Web of Science up to the cutoff date 18 October 2021.
RESULTS
Twenty-five articles out of the 6547 initially detected publications were identified. Relevant medication-gene interactions were noted for drug safety. Interactions important for pain management were detected for (1) ibuprofen/; (2) celecoxib/; (3) piroxicam/, ; (4) diclofenac/, , , ; (5) meloxicam/; (6) aspirin/, , and ; (7) amitriptyline/ and ; (8) imipramine/; (9) nortriptyline/, , ; and (10) escitalopram/, , and .
CONCLUSIONS
Overall, a lack of well powered human in vivo studies assessing the pharmacogenetics in pain patients treated with NSAIDs or antidepressants is noted. Studies indicate a higher risk for partly severe side effects for the poor metabolizers and NSAIDs. Further in vivo studies are needed to consolidate the relevant polymorphisms in NSAID safety as well as in the efficacy of NSAIDs and antidepressants in pain management.
PubMed: 35745763
DOI: 10.3390/pharmaceutics14061190 -
Clinical Pharmacology and Therapeutics Dec 2022Pharmacogenomic (PGx) testing has emerged as a compelling strategy that clinicians can use to inform antidepressant medication selection and dosing, but the clinical... (Meta-Analysis)
Meta-Analysis
Pharmacogenomic (PGx) testing has emerged as a compelling strategy that clinicians can use to inform antidepressant medication selection and dosing, but the clinical efficacy of this strategy has been questioned. We systematically reviewed and meta-analyzed clinical trials for an association between the use of PGx-guided antidepressant therapy and depressive symptom remission in patients with major depressive disorder (MDD). We included prospective, controlled clinical trials published in English up to July 12, 2022. Data extraction and synthesis adhered to the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Each trial was assessed for risk of bias and a random-effects model was used to estimate pooled risk ratios. Thirteen trials comprising 4,767 patients were analyzed, including 10 randomized controlled trials, and three open label trials. Across all included trials, those that received PGx-guided antidepressant therapy (n = 2,395) were 1.41 (95% confidence interval (CI) = 1.15-1.74, P = 0.001) more likely to achieve remission compared with those that received unguided antidepressant therapy (n = 2,372). Pooled risk ratios for randomized controlled trials and open label trials were 1.46 (95% CI: 1.13-1.88) and 1.26 (95% CI = 0.84-1.88), respectively. These results suggest that PGx-guided antidepressant therapy is associated with a modest but significant increase in depressive symptom remission in adults with MDD. Efforts to address the heterogeneity in PGx test composition (i.e., genes and alleles tested) and accompanying prescribing recommendations across trials will likely reduce the uncertainty about the efficacy of PGx-guided antidepressant therapy in the literature.
Topics: Adult; Humans; Antidepressive Agents; Depression; Depressive Disorder, Major; Pharmacogenomic Testing; Prospective Studies; Randomized Controlled Trials as Topic
PubMed: 36111494
DOI: 10.1002/cpt.2748 -
Journal of Personalized Medicine Jun 2023This systematic review evaluated the animal and human evidence for pharmacomicrobiomics (PMx) interactions of antidepressant medications. Studies of gut microbiota... (Review)
Review
This systematic review evaluated the animal and human evidence for pharmacomicrobiomics (PMx) interactions of antidepressant medications. Studies of gut microbiota effects on functional and behavioral effects of antidepressants in human and animal models were identified from PubMed up to December 2022. Risk of bias was assessed, and results are presented as a systematic review following PRISMA guidelines. A total of 28 (21 animal, 7 human) studies were included in the review. The reviewed papers converged on three themes: (1) Antidepressants can alter the composition and metabolites of gut microbiota, (2) gut microbiota can alter the bioavailability of certain antidepressants, and (3) gut microbiota may modulate the clinical or modeled mood modifying effects of antidepressants. The majority (n = 22) of studies had at least moderate levels of bias present. While strong evidence is still lacking to understand the clinical role of antidepressant PMx in human health, there is evidence for interactions among antidepressants, microbiota changes, microbiota metabolite changes, and behavior. Well-controlled studies of the mediating and moderating effects of baseline and treatment-emergent changes in microbiota on therapeutic and adverse responses to antidepressants are needed to better establish a potential role of PMx in personalizing antidepressant treatment selection and response prediction.
PubMed: 37511699
DOI: 10.3390/jpm13071086 -
Research in Social & Administrative... Nov 2023The field of pharmacogenomics is rapidly advancing, but its adoption and implementation remain slow and lacking. Lack of pharmacogenomics knowledge among healthcare... (Review)
Review
BACKGROUND
The field of pharmacogenomics is rapidly advancing, but its adoption and implementation remain slow and lacking. Lack of pharmacogenomics knowledge among healthcare professionals is the most frequently cited barrier to adopting and implementing pharmacogenomics in clinical settings.
OBJECTIVES
This study aimed to critically evaluate and determine the effectiveness of educational interventions in improving pharmacogenomics knowledge and practice.
METHODS
Four electronic databases were searched: MEDLINE, EMBASE, CENTRAL, and PsycINFO. Studies on pharmacogenomics educational interventions for health care professionals and students with pre- and post-intervention assessments and results were included. No restrictions were placed on time, language, or educational contexts. The educational outcomes measured include both objective and subjective outcomes. The pharmacogenomics competency domains used to judge educational interventions are based on the competency domains listed by the American Association of Colleges of Pharmacies (AACP). The National Heart, Lung, and Blood Institute of the National Institutes of Health was used for the quality assessment of pre-post studies with no control group and the controlled intervention studies. No meta-analysis was conducted; the data were synthesized qualitatively. The systematic review was reported in accordance with the PRISMA statement.
RESULTS
Fifty studies were included in this review. All included studies integrated the AACP pharmacogenomics competency domains into their educational interventions. Most of the studies had educational interventions that integrated clinical cases (n = 44; 88%). Knowledge was the most frequently evaluated outcome (n = 34; 68%) and demonstrated significant improvement after the educational intervention that integrated AACP pharmacogenomics competency domains and employed active learning with clinical case inclusion.
CONCLUSION
This review provided evidence of the effectiveness of educational interventions in improving pharmacogenomics knowledge and practice. Incorporating pharmacogenomics competency domains into education and training, with patient cases for healthcare professionals and students, dramatically improved their pharmacogenomics knowledge, attitudes, and confidence in practice.
Topics: Humans; Pharmacogenetics; Students; Health Personnel; Educational Status; Delivery of Health Care
PubMed: 37586945
DOI: 10.1016/j.sapharm.2023.07.012 -
The Pharmacogenomics Journal Jul 2022Although clozapine is the most effective pharmacotherapy for treatment-resistant schizophrenia, it is under-utilized, and initiation is often delayed. One reason is the... (Meta-Analysis)
Meta-Analysis
Although clozapine is the most effective pharmacotherapy for treatment-resistant schizophrenia, it is under-utilized, and initiation is often delayed. One reason is the occurrence of a potentially fatal adverse reaction, clozapine-induced agranulocytosis (CIA). Identifying genetic variations contributing to CIA would help predict patient risk of developing CIA and personalize treatment. Here, we (1) review existing pharmacogenomic studies of CIA, and (2) conduct meta-analyses to identify targets for clinical implementation. A systematic literature search identified studies that included individuals receiving clozapine who developed CIA and controls who did not. Results showed that individuals carrying the HLA-DRB1*04:02 allele had nearly sixfold (95% CI 2.20-15.80, p = 0.03) higher odds of CIA with a negative predictive value of 99.3%. Previously unreplicated alleles, TNFb5, HLA-B*59:01, TNFb4, and TNFd3 showed significant associations with CIA after multiple-testing corrections. Our findings suggest that a predictive HLA-DRB1*04:02-based pharmacogenomic test may be promising for clinical implementation but requires further investigation.
Topics: Agranulocytosis; Alleles; Antipsychotic Agents; Clozapine; Humans; Pharmacogenetics; Pharmacogenomic Testing
PubMed: 35710824
DOI: 10.1038/s41397-022-00281-9 -
Cancer Reports (Hoboken, N.J.) Jan 2023Accumulating studies have evaluated the association between MAP3K1 polymorphisms and cancer prognosis. However, the results of these studies are conflicting. Given the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Accumulating studies have evaluated the association between MAP3K1 polymorphisms and cancer prognosis. However, the results of these studies are conflicting. Given the potential impact of MAP3K1 rs889312 SNP on the prognosis of various cancers, this meta-analysis was performed to obtain solid and credible evidence.
METHODS AND MATERIALS
This study was performed according to the PRISMA 2020 statement. A comprehensive article search was conducted to find and select articles from multiple databases, including PubMed, Google Scholar, Web of Science, EMBASE and the Cochrane Library, published up to 15th September 2022. The data analysis was performed with Review Manager v5.2. Pooled HR with its 95% CI and p-value was calculated where HR >1 suggests worse/poor survival and HR <1 suggests better survival of cancer patients.
RESULTS
A total of five articles comprising 24 439 patients were included for both qualitative and quantitative data synthesis. It was found that only the dominant genetic model (AC + CC vs. AA) showed a statistically significant poor overall survival for MAP3K1 rs889312 polymorphism (HR = 1.25, 95% CI = 1.06-1.47, p = .01). In addition, publication bias analysis by the Egger's test and the Begg-Mazumdar test reported no significant bias in the analysis of overall survival (p > .05).
CONCLUSIONS
The present study concludes that MAP3K1 gene rs889312 polymorphism plays a prognostic role in the survival of cancer patients. However, future research is recommended that will analyze more MAP3K SNPs along with rs889312, which may reveal more credible outcomes in terms of cancer prognosis.
Topics: Humans; Neoplasms; Polymorphism, Single Nucleotide; Prognosis; MAP Kinase Kinase Kinase 1
PubMed: 36560873
DOI: 10.1002/cnr2.1773 -
Clinical and Translational Science Dec 2023Clinical implementation of pharmacogenomic (PGx)-guided prescribing in oncology lags behind research evidence generation. We aimed to identify healthcare professionals'... (Review)
Review
Clinical implementation of pharmacogenomic (PGx)-guided prescribing in oncology lags behind research evidence generation. We aimed to identify healthcare professionals' (HCPs) and consumers' knowledge, attitudes, perspectives, and education needs to inform strategies for implementation of scalable and sustainable oncology PGx programs. Systematic review of original articles indexed in EMBASE, EMCARE, MEDLINE, and PsycInfo from January 2012 until June 2022, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and using the Mixed Methods Appraisal Tool. PROSPERO registration number CRD42022352348. Of 1442 identified studies; 23 met inclusion criteria with 87% assessed high quality. Of these, 52% reported on HCPs, 35% on consumers, and 13% on both HCPs and consumers. Most were conducted in the United States (70%) and included multiple cancer types (74%). Across studies, HCPs and consumers mostly perceived value in PGx, however, both groups reported barriers to utilization, including cost, lack of consistent recommendations across guidelines, and limited knowledge among HCPs; test accuracy, clear testing benefits, and genomic information confidentiality among consumers. HCPs and consumers value and want to engage in PGx strategies in oncology care, however, are inhibited by unmet needs and practice and knowledge gaps. Implementation strategies aimed at addressing these issues may best support increased PGx uptake in oncology practice.
Topics: Humans; Pharmacogenetics; Health Knowledge, Attitudes, Practice; Health Personnel; Medical Oncology; Neoplasms
PubMed: 37991131
DOI: 10.1111/cts.13672